The objective of the research is to determine the mechanism by which membrane enzymes are regulated in aging and development. It has been shown that triiodothyronine and triamcinolone administration reverse age related changes in the specific activity of the endoplasmic reticulum enzyme glucose-6-phosphatase. The enzyme apparently consists of a transport component which delivers the substrate to a hydrolytic component localized on the inner surface of the membrane; these may represent separate polypeptide chains, since the two components respond separately to hormonal deprivation and stimulation. The mechanism by which the hepatocyte exhibits a different response in old animals compared to young is being studied. The relationship between membrane structure and the function of glucose-6-phosphatase and other membrane-bound enzymes is investigated. Attempts are in progress to identify and purify the protein responsible for glucose-6-phosphate hydrolysis, and then determine the role of protein synthesis and protein degradation in the regulation of enzymatic activity. The investigation is planned as a first step towards understanding the role played by membranes in aging and development. BIBLIOGRAPHIC REFERENCES: Latency of Inosine-5'-diphosphatase in microsomes isolated from rat liver. J.S. Little, D.R. Thiers and C.C. Widnell (1976) J. Biol. Chem. 251 7821-7825. Membranes involved in exocytosis and endocytosis: a cytochemical approach. C.C. Widnell and J.S. Little (1977). In Membranous Elements and Movement of Molecules: Techniques. E. Reid, ed. Horwood, Chichester, U.K. pp 149-162.